Abstract
BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the most intractable cancers, so the development of novel therapeutics has been required to improve patient outcomes. Curcumin, a polyphenol from Curcuma longa, exhibits various health benefits including antitumor effects, but its clinical utility is limited because of low bioavailability. Theracurmin® (THC) is a highly bioavailable curcumin dispersed with colloidal submicron particles.MethodsWe examined antitumor effects of THC on ESCC cells by cell viability assay, colony and spheroid formation assay, and xenograft models. To reveal its mechanisms, we investigated the levels of reactive oxygen species (ROS) and performed microarray gene expression analysis. According to those analyses, we focused on NQO1, which involved in the removal of ROS, and examined the effects of NQO1-knockdown or overexpression on THC treatment. Moreover, the therapeutic effect of THC and NQO1 inhibitor on ESCC patient-derived xenografts (PDX) was investigated.ResultsTHC caused cytotoxicity in ESCC cells, and suppressed the growth of xenografted tumors more efficiently than curcumin. THC increased ROS levels and activated the NRF2–NMRAL2P–NQO1 expressions. Inhibition of NQO1 in ESCC cells by shRNA or NQO1 inhibitor resulted in an increased sensitivity of cells to THC, whereas overexpression of NQO1 antagonized it. Notably, NQO1 inhibitor significantly enhanced the antitumor effects of THC in ESCC PDX tumors.ConclusionsThese findings suggest the potential usefulness of THC and its combination with NQO1 inhibitor as a therapeutic option for ESCC.
Highlights
Esophageal squamous cell carcinoma (ESCC) is the major histological type of esophageal cancer [1, 2], which is the sixth leading cause of cancer-related mortality and the eighth most common cancer worldwide [3, 4]
We focused on NAD(P)H quinone dehydrogenase 1 (NQO1), which involved in the removal of reactive oxygen species (ROS), and examined the effects of NQO1-knockdown or overexpression on THC treatment
NQO1 inhibitor significantly enhanced the antitumor effects of THC in ESCC patient-derived xenografts (PDX) tumors. These findings suggest the potential usefulness of THC and its combination with NQO1 inhibitor as a therapeutic option for ESCC
Summary
Esophageal squamous cell carcinoma (ESCC) is the major histological type of esophageal cancer [1, 2], which is the sixth leading cause of cancer-related mortality and the eighth most common cancer worldwide [3, 4]. The development of novel treatment options has been needed to improve the outcomes for ESCC patients. Curcumin has been shown to have antitumor effects on several types of cancer cells including lung cancer [10], glioblastoma [11], colon cancer [12], pancreatic cancer [13], prostate cancer [14], and ESCC [15,16,17]. Esophageal squamous cell carcinoma (ESCC) is one of the most intractable cancers, so the development of novel therapeutics has been required to improve patient outcomes. A polyphenol from Curcuma longa, exhibits various health benefits including antitumor effects, but its clinical utility is limited because of low bioavailability. TheracurminÒ (THC) is a highly bioavailable curcumin dispersed with colloidal submicron particles
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call